Báo cáo y học: Presence of a functional but dispensable Nuclear Export Signal in the HTLV-2 Tax protein

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Presence of a functional but dispensable Nuclear Export Signal in the HTLV-2 Tax protein
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Báo cáo y học: " Presence of a functional but dispensable Nuclear Export Signal in the HTLV-2 Tax protein"Retrovirology BioMed Central Open AccessResearchPresence of a functional but dispensable Nuclear Export Signal inthe HTLV-2 Tax proteinSébastien A Chevalier1, Laurent Meertens1, Sara Calattini1, Antoine Gessain1,Lars Kiemer2 and Renaud Mahieux*1Address: 1Unité dEpidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, France and 2Center for Biological SequenceAnalysis, BioCentrum-DTU, The Technical University of Denmark, Building 208 DK-2800, Lyngby, DenmarkEmail: Sébastien A Chevalier - schevali@pasteur.fr; Laurent Meertens - lmeerten@aecom.yu.edu; Sara Calattini - scalatt@pasteur.fr;Antoine Gessain - agessain@pasteur.fr; Lars Kiemer - lars@cbs.dtu.dk; Renaud Mahieux* - rmahieux@pasteur.fr* Corresponding authorPublished: 14 November 2005 Received: 14 October 2005 Accepted: 14 November 2005Retrovirology 2005, 2:70 doi:10.1186/1742-4690-2-70This article is available from: http://www.retrovirology.com/content/2/1/70© 2005 Chevalier et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Human T-cell leukemia virus type 1 and type 2 are related human retroviruses. HTLV-1 is the etiological agent of the Adult T-cell Leukemia/Lymphoma and of the Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy, whereas, HTLV-2 infection has not been formally associated with any T-cell malignancy. HTLV-1 and 2 genomes encode, respectively, the Tax1 and Tax2 proteins whose role is to transactivate the viral promoter. HTLV-1 and HTLV-2 Tax sequences display 28% divergence at the amino acid level. Tax1 is a shuttling protein that possesses both a non canonical nuclear import (NLS) and a nuclear export (NES) signal. We have recently demonstrated that Tax1 and Tax2 display different subcellular localization and that residues 90– 100 are critical for this process. We investigate in the present report, whether Tax2 also possesses a functional NES. Results: We first used a NES prediction method to determine whether the Tax2 protein might contain a NES and the results do suggest the presence of a NES sequence in Tax2. Using Green Fluorescent Protein-NES (GFP-NES) fusion proteins, we demonstrate that the Tax2 sequence encompasses a functional NES (NES2). As shown by microscope imaging, NES2 is able to mediate translocation of GFP from the nucleus, without the context of a full length Tax protein. Furthermore, point mutations or leptomycin B treatment abrogate NES2 function. However, within the context of full length Tax2, similar point mutations in the NES2 leucine rich stretch do not modify Tax2 localization. Finally, we also show that Tax1 NES function is dependent upon the positioning of the nuclear export signal vis-à-vis GFP. Conclusion: HTLV-2 Tax NES is functional but dispensable for the protein localization in vitro. ological agent of the Adult T-cell Leukemia/LymphomaBackgroundHTLV-1 and HTLV-2 are closely related retroviruses that (ATLL) and of the Tropical Spastic Paraparesis/HTLV-1infect T-cells in vivo, with a probable preferential tropism Associated Myelopathy (TSP/HAM), while HTLV-2 infec-for CD4+ and CD8+ cells respectively [1]. HTLV-1 is the eti- tion, even if originally described in a patient suffering of Page 1 of 11 (page number not for citation purposes)Retrovirology 2005, 2:70 http://www.retrovirology.com/content/2/1/70atypical hairy T-cell leukemia, has ...